ADAPTATIONS OF VERTEBRATE NEURONS TO HYPOXIA AND ANOXIA - MAINTAININGCRITICAL CA2+ CONCENTRATIONS

Down-regulation of ion channel activity ('channel arrest'), which aids in preserving critical ion gradients in concert with greatly diminish ed energy production, is one important strategy by which anoxia-tolera nt neurons adapt to O-2 shortage. Channel arrest results in the elimin ation of action potentials and neurotransmission and also decreases th e need for ion transport, which normally requires a large energy expen diture. Important targets of this downregulation may be channels in wh ich activity would otherwise result in the toxic increases in intracel lular [Ca2+] characteristic of anoxia-sensitive mammalian neurons. In turtles, Na+ channels and the Ca2+-permeable ion channel of the N-meth yl-D-aspartate (NMDA)-type glutamate receptor undergo down-regulation during anoxia, Inactivation of NMDA receptors during hypoxia occurs by a variety of mechanisms, including alterations in the phosphorylation state of ion channel subunits, Ca2+ dependent second messenger activa tion, changes in Ca2+-dependent polymerization/depolymerization of act in to postsynaptic receptors and activation of other G-protein-coupled receptors, Release of inhibitory neurotransmitters (e.g. gamma-aminob utyrate) and neuromodulators (e.g. adenosine) into the brain extracell ular fluids may play an important role in the down-regulation of these and other types of ion channels.